Efficacy of clozapine versus second-generation antipsychotics in people with treatment-resistant schizophrenia: a systematic review and individual patient data meta-analysis

作者：Johannes Schneider‐Thoma, Tasnim Hamza, Konstantina Chalkou, Spyridon Siafis, Shimeng Dong, Irene Bighelli, Wulf‐Peter Hansen, Elfriede Scheuring, John M. Davis, Josef Priller, Pierre Baumann, Robert R. Conley, Joachim Cordes, Deanna Kelly, Michael Kluge, Sanjiv Kumra, Shôn Lewis, Herbert Y. Meltzer, Dieter Naber, Nina R. Schooler, Jan Volavka, Kristian Wahlbeck, Georgia Salanti, Stefan Leucht · 发表于：The Lancet Psychiatry · 年份：2025 · DOI：10.1016/s2215-0366(25)00001-x · 被引用次数：31 · 研究领域：Schizophrenia research and treatment、Mental Health and Psychiatry、Healthcare Decision-Making and Restraints

BACKGROUND: Clozapine is recommended by national and international guidelines for people with treatment-resistant schizophrenia. However, available meta-analyses of randomised controlled trials have not shown superior efficacy of clozapine when compared with other second-generation antipsychotics, with heterogeneity identified between the original studies. We aimed to use individual patient data (IPD) to account for potential reasons of variability and to synthesise an adjusted estimate for the difference in efficacy between clozapine and other second-generation antipsychotics for treatment-resistant schizophrenia. METHODS: In this systematic review and IPD meta-analysis, we searched the Cochrane Schizophrenia Group's Study-Based Register from inception to Jan 24, 2024, and previous reviews for blinded randomised controlled trials comparing clozapine with other second-generation antipsychotics in participants with treatment-resistant schizophrenia. Trials were eligible if they included patients with treatment-resistant schizophrenia and had a duration of at least 6 weeks. IPD were requested from trial investigators. The primary outcome was change in overall schizophrenia symptoms as measured by the Positive and Negative Syndrome Scale (PANSS) between clozapine and other second-generation antipsychotics after 6-8 weeks of treatment. The effect size measure for the primary outcome was mean difference with 95% credible interval (CrI). We fitted a Bayesian random-effects IPD meta...